17-28910268-C-T

Position:

• chr17-28910268-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001033561.2(PHF12):​c.2317G>A​(p.Val773Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHF12 NM_001033561.2 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 2.88

Genes affected

PHF12 (HGNC:20816): (PHD finger protein 12) Enables phosphatidylinositol binding activity and transcription corepressor activity. Involved in negative regulation of transcription, DNA-templated. Acts upstream of or within negative regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of Sin3 complex and transcription repressor complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09594977).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHF12	NM_001033561.2	c.2317G>A	p.Val773Ile	missense_variant	11/15	ENST00000332830.9	NP_001028733.1
PHF12	NM_001290131.2	c.2317G>A	p.Val773Ile	missense_variant	11/11		NP_001277060.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHF12	ENST00000332830.9	c.2317G>A	p.Val773Ile	missense_variant	11/15	2	NM_001033561.2	ENSP00000329933.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

PHF12-related disorder Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 22, 2024

The PHF12 c.2317G>A variant is predicted to result in the amino acid substitution p.Val773Ile. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.087	T;.;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.060
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.59	T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.096	T;T;T
MetaSVM	Uncertain	0.090	D
MutationAssessor	Benign	1.5	L;L;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.31	N;.;.
REVEL	Benign	0.24
Sift	Benign	0.13	T;.;.
Sift4G	Benign	0.21	T;T;.
Polyphen		0.0010	B;.;.
Vest4		0.20
MutPred		0.11		Gain of glycosylation at S772 (P = 0.1907);Gain of glycosylation at S772 (P = 0.1907);.;
MVP		0.19
MPC		0.21
ClinPred		0.21	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.026
gMVP		0.16

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-27237286;